The triad of dermatologic lesions, including fibrofolliculomas, trichodiscomas and achrocordons, known as the Birt-Hogg-Dubé (BHD) syndrome, was originally described in a Canadian kindred in 1977 (Birt et al., Arch. Dermatol. 113:1674-1677, 1977). Other phenotypic features were found to be associated with BHD syndrome including renal neoplasia (Roth et al., J. Amer. Acad. Derm. 29:1055-1056, 1993) and lung cysts and/or spontaneous pneumothorax (Toro et al., Arch Dermatol. 135:1195-1202, 1999). When adjusted for age, patients with fibrofolliculomas (benign tumors of the hair follicle) have about a seven-fold increased risk for developing renal neoplasms and a 50-fold increased risk for developing spontaneous pneumothorax compared with their unaffected siblings. Lung cysts develop frequently (83%) in affected members of BHD families (Zbar et al., Cancer Epidem. Bio. Prev. 11:393-400, 2002). Although colon polyps have been reported in BHD patients (Hornstein et al., Hum. Genet. 33:193-197, 1976; Hornstein et al., Arch. Derm. Res. 253:161-175, 1975), the frequency is not statistically significant compared to unaffected siblings (Zbar et al., Cancer Epidem. Bio. Prev. 11:393-400, 2002). Previously, the present inventors used the original BHD family of Birt, Hogg and Dubé to perform a genome-wide scan for linkage and localized the disease gene locus by linkage analysis in 8 additional families to a 4 cM region of chromosome 17p11.2 between D17S1857 and D17S805 (Schmidt et al., Am. J. Hum. Genet. 69:876-882, 2001). Linkage to 17p12-q11.2 was also reported in a Swedish BHD pedigree with associated renal neoplasms (Khoo et al., Oncogene 20, 5239-5242, 2001). The BHD encoding sequence, however, is unknown.